A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium

Summary

Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances.

Introduction

Cryptosporidium was identified as a cause of human infection in 1976.¹ During the early 1980s, cryptosporidiosis was recognised as the major cause of chronic diarrhoea in patients with AIDS, as a cause of zoonotic and waterborne outbreaks of diarrhoea, and as a cause of diarrhoea in children.2, 3, 4, 5 By the mid-1990s, cryptosporidium was known to be ubiquitous and was linked with childhood malnutrition and premature death in low-resource settings. A massive waterborne epidemic affected more than 400 000 people in Milwaukee, WI, USA, in 1993.⁶ Despite this knowledge, cryptosporidiosis is substantially under-recognised and underdiagnosed, treatments are suboptimum, and preventive measures are incomplete. Even in settings such as the USA where modern diagnostics are widely available, estimates state that only about 1% of cases are diagnosed and reported.⁷

Recent advances in knowledge are shifting opinions of the epidemiology of cryptosporidiosis, and have increased estimates of the global burden of disease.⁸ To identify potential gaps and opportunities for future studies, the US Foundation for the National Institutes of Health convened a group of experts to discuss advances in the epidemiology, diagnosis, therapeutics, and immunisation for cryptosporidiosis. In this Review, we summarise discussions of this meeting, and provide a more in-depth review of published research.